Data from a number of investigators suggests that there may be a direct relationship between the renin-angiotensin-aldosterone system and the kallikrein-kinin system. We wish to determine if individual portions of the renin-angiotensin system including metabolites of angiotensin II influence renal or urinary kallikrein. We also wish to determine if bradykinin or kallidin influence kallikrein through a feedback-type mechanism. We also wish to determine if urinary kallikrein accurately reflects renal kallikrein in experimental circumstances and if kallikrein esterase activity accurately reflects the kallikrein "kinin-forming activity (kininogenase). To study these problems, particularly whether individual components of the renin-angiotensin system or bradykinin or kallidin influence renal and urinary kallikrein in an in vivo preparation, we plan to infuse these agents into an autoperfused rat kidney. This preparation will also allow us to determine the relationship between the infused substances and renal blood flow, glomerular filtration rate, sodium, potassium, and water excretion from the kidney, and systemic blood pressure as well as to kallikrein and perhaps kinins. Renal and urinary kallikrein will be measured both by the 3H-TAME (exterolytic activity) method and by the ability of these kallikreins to generate kinins when reacted with exogenous kininogen. Kinin production will be measured by bioassay utilizing guinea pig ileum or by radioimmunoassay. If components of the renin angiotensin system are found to influence renal or urinary kallikrein production or secretion, further experimets will be done in which we will indirectly assess the influence of this system by administration of pharmacologic agents or by creating physiologic situations which alter renal-renin activity. Such measures include the administration of beta blocking agents, hydralazine or diuretics, and dietary sodium restriction or sodium loading. These studies will lead to an improvement in our understanding of kallikrein metabolism and function in normotensive states and should lead to further understanding of the possible role of the kallikrein-kinin system in the development and maintenance of hypertension.